Immunodeifciencys Flashcards
What are immunodeficiency’s?
Caused by defects in immune system components
May lead too seriously an often fatal syndromes or diseases
Classified as primary and secondary
Difficult to estimate at birth
What are PRIMARY (congenital) immunodeficiency’s (PID)?
A condition resulting from a genetic or developmental defect
Defect present FROM BIRTH n it mostly inherited
May not be observed NTS later in life
What are SECONDARY immunodeficiency’s?
Reignite as a result of malnutrition, cancer, drug treatment or infection
By far the most well known and commonly occurring is AIDS
What are the lineal features of primary immunodeficiency’s?
Reaccurent infections
Severe infections, unusual pathogen (that wont usually cause a immune response) , unusual sites
There are 10 warning signs - 2 or more indicate PID
What causes PID?
May effect either innate or adaptive immune function
Defects in innate immunity are generally caused by a defect in phagocytise or complement function.
Lymphoid cell disorders may effect T cells or B cells
What is the relation between PID and haematopoesis?
Defects in the earlier stem cells affect the entire Immune system
Defects in later stage haematopoietic cells show a more restricted pathology
REVISION ACTIVITY
DRAW A TREE DIAGRAM FROM THE SLIDE IN THE LECTURE OF HAEMATOPPOEIISIS AND MAKE. MIND-MAP LINKING THE CELLS WTH OTHER LECTURES AND THE FUNCTIONS OF EACH COLOUR GROUP OF CELLS
What are the defects in adaptive immunity that can cause PID?
B cells, T cells combined
T cell defects impair antibody function
Defects in lymphocyte development or activation
What are the major B cell disorder of PID?
Brutons disease (x linked a gamma globulin anaemia)
Common variable deficiency (CVID)
Selective IgA deficiency
igG2 subclass deficiency
Specific ig deficiency with normal igs
What is Brutons disease?
Defect in BTK gene. - located on X chromosome
Encodes Britons tyrosine kinase - important in signalling downstream pre-B cell receptor too become mature B cells
Bock in B-cell development when gene is mutated
Reaccurant severe bacterial infections
35% develop autoimmune conditions
How is Brutons disease diagnosed?
B cells abscent/ low; plasma cells abscent
All immunoglobulins abscent / very low
T cells and T cell-mediated responses normal
Diagnosed using immunoelectrophoresis an flow cytometry
How is Brutons disease treated?
IVIg
OR subcutaneous Ig weekly
Prompt antibiotic therapy (URI/LRI)
Do not give live-attenuated vaccines
What is igA selective deficiency?
Most common
Most cases asymptomatic; some infections of Respiratory, urogenital or gastrointestinal
Low levels serum and secretory igA
Sometimes increased incidence allergic disease
What is combined immunodeficiency’s?
Severe combined immunodeficiency (SCID)
- immmnoglobids are low
- affect T,B NK cells
- T cell function reduced and cytokine production
Predominant T cell disorders.
What causes severe combined immunodeficiency SID?
Common cytokine receptor gamma chain defect (IL-2, IL-4, IL-7).
IL-7 needed for survival T cell precursors resulting in defective T cell development and concomitant lack in B cell help (low antibodies)
RAG-1/RAG-2 defect = no T and B cells
ADA = cumulative of deoxyadenosine + deoxy-ADP which is toxic for rapidly dividing thymocytes
IL-2 important for cytotoxic T cell survival
How is SCID diagnosed?
Flow cytometry
- low or no NK cells
- low or no T cells
- low or no B cells
How is SCID treated?
Patient isolation - in a sterile environment - Server impact on quality of life
Do not give live vaccines
Blood products from CMV-negative donors
IV ig replacement
Infection prohylaxis
Bone marrow/haematopoietic stem cell transplant
Gene therapy
What is the outcome of SCID?
Depend on promptness of diagnosis
Survival > 80% - EARLY DIAGNOSIS, GOOD DONOR MATCH, NO INFECTIONS PRE TRANSPLANT
Survival < 40% - LATE DIAGNOSIS, CHRONIC INFECTIONS, POORLY MATCHED DONORS
Regular monitors post BMT (Bone marrow transplant) = engraftment
What is DiGeorge syndrome?
Thymidine hypoplasia dur to 22q11 deletion
Results in Faliure development 3+4 pharyngeal pouches
Dysmorphic face, low set ears, fish shaped mouth
Hypocalcaemia, cardiac abnormalities
Variable immunodeficiency’s - partial or absent T cell development
What is the treatment fr DiGeorge syndrome?
Thymus transplantation (GOSH).
Not perminant but do provide patient with a few years of good quality life
What is Wiskott-Aldrich syndrome?
X linked
Defect in WASP - protein involved in actin polymerisation - T cells remodel cytoskeleton for correct signalling
Thrombocytopenia, eczema and infections
Progressive immunodeficiency (T cell loss and decreased proliferation)
Antibody production
What are 3 types of innate immunodeficiency disorders?
Chronic granulomatous disease
Chediak higashi syndrome
Leukocyte adhesion deficiency
What defects of the innate immune system can cause PID?
Phagocyte defects
- Quantitative - low number of phagocytes
- Qualitative - altered function
Recruitment defects
- transmigration defects
Complement defects
what happens in chronic granulomatous disease (CGD) ?
Formation of granulomas
Caused by Defective oxidative killing of phagocytoses microbe
Mutation in phagocyte oxidase (NADPH) components
NADPH are needed to generate superoxide anion to destroy pathogens when engulfed by macrophages
How is CGD diagnosed?
Nitro blue tetrazolium reduction test
- NADH dye
- patient who does have it (pink)
Flow cytometry
- dihydrohodamine assay
- will remain in a resting state in CGD patient
What is Chediak-Higashi syndrome?
Rare genetic disease
defect in LYST gene (regulates lysosome traffic)
Neutrophils have defective phagocytosis
Repetitive, severe infections
How is Chediak-higashi syndrome diagnosed?
Decreased number of neutrophils
Neutrophils have giant granules
What is Leukocyte adhesion deficiency (LAD)?
Normally leukocytes are recruited from the blood stream to the site of infection
Defect in beta 2 chain integrins (LFA-1, Mac-1)
Defect in selection ligand
Delayed umbilical cord separation = diagnosis defect in beta 2 chain integrins
Presented by skin, GIT infections and perinatal ulcers
How is LAD diagnosed?
Low neutrophil chemotaxis
Low integrins expression on phagocytes (Flow cytometry)
What is the aim of PID treatments?
Minimise/control infection
Prompt treatment of infection
Prevention of infection: isolation, antibiotic prophylaxis, NON LIVE vaccines
Nutrition
Replace defective/absent component of the immune system
Gene therapy - stem cell and bone marrow treatment
What can cause secondary or aquired immunodeficiencies?
HIV infection - depletion of CD4 cells
Malnutrition - metabolic derangements inhibit lymphocyte maturation
Cancer metastasis and leukaemia
Removal of spleen - decreased phagocytosis
Immunosuppression for transplants
What is the more common type of immunodeficiency?
Secondary immunodeficiencies
What occurs using HIV-AIDS?
- Vern binding to CD4 and chemokine receptor
- Fusion of HIV membrane with cell membrane, entry of viral genome into cytoplasm
- Reverse transcription
- Integration of provirus into genome
- Cytokine activationn of cel - transcription of HIV genome
- Synthesis oof HIV proteins
- Expression of antigens on surface and budding off of mature virus
- CD4 cell depletion over time
What is AIDS defined as?
When the number of CD4 cells is lower than the number of viral cells
Infections are the major cause of death in AIDS patients
How can HIV-AIDS be treated?
HAART - prevents AIDS occurring
PrEP - stops transmission
